DESCRIPTION: (Applicant's Description) The purpose of this Academic Research Career Award in Preventive Oncology is to provide the candidate, Patrick Paul Koty, funding to support his salary while he continues to develop his skills as an educator and researcher in the field of preventive oncology. His knowledge of human genetics and expertise in cytogenetic, molecular cytogenetic, and molecular genetic approaches to investigating the etiology of human disease provides an excellent foundation upon which to build a career as an independent investigator and academician. His immediate career goals are to continue developing his knowledge of the process of carcinogenesis for the prevention of disease and refine his oratory and writing skills. His long term goal is to become as an independent investigator in an academic environment dedicated to developing approaches for the prevention and control of lung carcinogenesis. The Allegheny University of the Health Sciences provides an excellent academic and research environment for Dr. Koty to develop his career in preventive oncology. His Mentoring Committee (Drs. Levitt, Shackney, Pyeritz, and Estop) are renowned experts in their respective fields including lung carcinogenesis, cancer, and human genetics, and will provide him the mentoring necessary to attain his career goals. The career development plan for Dr. Koty will concentrate on several areas: 1) structured course work, 2) mentored writing, 3) teaching, 4) curriculum design, 5) technical workshops, 6) leadership skills, 7) ABMG certification, 8) ethics, and 9) research. Dr. Koty's research plan will investigate molecular mechanisms for the prevention of lung carcinogenesis, in particular the genetically regulated pathway of programmed cell death (PCD). The PCD pathway is altered in non-small cell lung cancer (NSCLC) cells resulting in resistance to chemotherapeutic agents which induce this process. Genes involved in the regulation of the PCD pathway are also altered in preneoplastic cells. Therefore, genetically manipulating these preneoplastic cells to reenter the PCD pathway may result in the prevention of NSCLC. Dr. Koty will investigate the role of several PCD regulatory genes (bcl-2, bax, bcl-x-l&s, and TGM2) in matched preneoplastic and primary malignant tissues from NSCLC patients, and NSCLC cell lines. The data obtained from these studies will also be used to develop a model for the process of programmed cell death. This model will be used to determine risk assessment for the development of non-small cell lung cancer.